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1
Principles of General and Autonomic Pharmacology
Dr. Edward JN IshacProfessor
Pharmacology Course DirectorDepartment of Pharmacology &
ToxicologySmith Bldg, Room 742
[email protected], x82127
Reference Material • Basic and Clinical Pharmacology by
Katzung, 11th ed., 2009, paperback (required text, new: $65, used: $49)http://www.library.vcu.edu/
• Goodman & Gilman’sPharmacological Basisof Therapeutics, 12th ed.2010 (optional text)(New: $170, Used: )
Paperback manual ($58,based on 11th ed.)
2
Pharmacology Syllabus
• Course material approx. 300 pages• Drug summary tables for available for
Pharmacology instructors.- Drug summary tables also available for faculty in other courses- Drug summary tables are not a substitute for syllabus, but list the main points or features- Understanding the drug summary Requires knowledge of syllabus
Principles of Pharmacology Faculty
Local anesthesia, CYP450Dr. Robinson
Toxicology introductionDr. CumpstonAntihistamines, herbal productsDr. Lichtman
Mechanisms of drug action, dose response, pharmacogenetics, drug modification, FDA regulation
Dr. DamajPain control, opioids, NSAIDs, PGsDr. Welch
Absorption, distribution, metabolism, excretion (ADME), drug interactions pharmacokinetics
Dr. Ritter
Autonomic pharmacology & NMJ, human simulation modules (new)
Dr. Ishac
3
Additional learning resources
• Micromedex and MD Consult These are drug and patient databases available through the VCU Library web
• Rx List www.rxlist.com
• Online Pharmacokinetics training module (Dr. Ritter)
• Online Cardiovascular modules (Dr. Ishac)
Alternate Pharmacology website
• http://www2.courses.vcu.edu/ptxed/ptx
• Contains: many practice questions (ANS), faqs, audio review of the cardiovascular system, online PowerPoint presentations, glossary. PDF and other downloads
• https://ecurriculum.som.vcu.edu/
4
Examinations and Grading • Final grade is determined by your
performance on all pharmacology questions during the year 2011-12
• Pharmacology questions are identified on each exam (Pharmtox). Questions will count as part of your grade in each course (GI, CNS, Renal, etc.,) and then combined to determine your final pharmacology grade.
Faculty
MicrobiologyNicholson
PrinciplesCardiovascular
Ishac
PrinciplesLichtman
MicrobiologyHylemon
Hem/OncologyGewirtz
PrinciplesDamaj
BehavioralBalster
CourseName
PrinciplesWomen’s Health
Welch
GIAkbarali
RespiratoryMiles
PrinciplesCNS
Robinson
PrinciplesCardiovascular
Ritter
PrinciplesCumpston
CourseName
5
Pharmacology Questions (Pharmtox)
303(1FCM)
105
19251426
920171242
499
2009-10
298(1FCM)
105
18241422
920171440
4100
2010-11
332151118272230
822171539
4104
2006-07
31110
919251336
821151239
4100
2008-09
339151017282428
822201746
4100
2007-08M2 Course
MusculoskeletalTotal Questions
GIWomen’s HealthBehavioral Sci. IICentral NSCardiovascularRespiratoryRenalEndocrineHematologyMicrobiologyPathogenesisPharmacology
Exam Results 2010-11
Total pharmacology questions in various courses = 298 (class avg = 86.4)
Total all M-II questions 1420(class avg = 83.7 – 92.0)
Pharmacology % of total – 21.0%
2010-11: Honors (41) High Pass (70)Pass (84) Marginal (0)Fail (0) Incomplete (3)
6
Pharmacology Examination
• Exam will be on Friday Aug. 12th in MSB• Curriculum office will announce time & duration• It will be a paper exam not electronic• The test will be multiple choice questions• It will consist of 100 MCQs, no True/False• You should bring a calculator; PDAs not allowed• Contains reference value table (back)• Most questions in USMLE Step 1 format• Drug trade names not included nor required
Cardiovascular & Pharmacokinetics, Pharmacokinetics Reviews (optional)
• Friday Aug. 5th, 12 noon in MSB (optional)• Dr. Ishac: Review autonomic agents and their effect
on the cardiovascular system• http://www2.courses.vcu.edu/ptxed/ptx/cv_ans.htm
• Monday Aug. 8th, 12 noon in MSB (optional)• Dr. Ritter:• Review principles of Pharmacokinetics (ADME)• Online Pharmacokinetics self-learn module (access
through eCurriculum)
7
Neuromuscular Blocking Agents - TBL• Dr. Ishac• Team-based Learning (TBL) session• Tuesday Aug 9th, 9:40am-11am• Use of “iClickers”• Use M-I group assignments• Complete reading assignment before class• Individual MCQ (6) test• Group MCQ test (same 6 questions)• MCQ question discussion appeal• General discussion question by group• Review of material
Human Simulation Module
• Drs. Ishac, Welch, Robinson & Cumpston• 10 possible Human Patient Simulation modules• View online overview (link on Resources page)• Sign-up online (SRS) by Fri Aug. 5th, 10pm • North Hospital, 2nd Floor, B218 (staging area)• Held Mon & Tue Aug 8-9th, 12:30pm-5pm (30 min
simulation session followed by 30 min debriefing)• Team groups of 5-6 for simulation module• 5 points towards your Pharmacology grade• Presented with 1 module of 10 for simulation• Reinforce concepts from class
8
Human Patient Simulation• Work in teams of 5-6
• Function as a health professional team
• 1 Lead Physician (patient history, present case, oversee team unity)
• 2-4 Secondary Physicians (perform PE exam ie. BP, HR, RR, O2, pupil response etc)
• 1 Pharmacist, laboratory specialist
• 1 Reporter (record history, PE exam values, laboratory values, treatments, present case)
Human Patient Module Cycle
• 0-5 min: Familiarize with manikin equipment and practice vital sign measurements.
• 5-25 min: Participation in simulation module (one of 10 modules)
• 25-30 min: Short debrief on performance as a health professional team
• 30-60 min: Formal debrief of two groups from different modules. Lead physician and reporter will present group case scenario and together with their team members answer questions and defend their decisions during the simulation module.
9
Human Patient Simulation - Manikin
Potential Human Simulation Roles
1.Lead physician2.Secondary physicians3.Pharmacist4.Nurse5.Physical assessor6.Laboratory specialist7.Reporter8.Patient companion9.Faculty facilitator
1 2,5
7
3,6
3,61 2,5
7
10
Laboratory tests and scans
Pharmacotherapy – Drug ToolboxBethanechol neostigmine physostigmineAtropine benztropine pralidoxime (2-PAM)Phentolamine propranolol metoprololEpinephrine norepinephrine clonidineDiphenhydramine dopamine haloperidolLabetalol fenoldopam phenoxybenzamineSuccinylcholine rocuronium acamprosateBupropion buspirone diazepamDisulfiram flumazenilHydroxyzine lorazepamMethadone morphineN-acetyl cysteine naloxoneNaltrexone thiamineVarenacline normal saline
11
Tips for Drug Learning• Learn agents by drug classes
ie. beta-blockers, Ca++-blockers etc
• Key points:- Clinical application - Mechanism of action - Drug of choice (DOC)
ie. epinephrine (anaphylaxis)- Prototype drugs, most common agents
ie. propranolol, atenolol, metoprolol- Important drug/drug interactions
ie. MAO inhibitors & tyramine rich food - Adverse drug reactions
ie. beta-blockers – asthma, Raynaud’s D.- Do not focus on dosage, know high/low Rx
Typical / Ideal Step 1 Exam QuestionA 42-old woman who is a biochemist is brought to the emergency department because of a 1-hour history of severe abdominal cramps, nausea, vomiting, sweating, and difficulty breathing due to bronchospasm and congestion. On physical examination her pulse is 45/min, BP is 85/50 mm Hg and she exhibits generalized muscle weakness. Laboratory studies show no abnormalities. Exposure to which of the following is most likely?
A. atropineB. bethanecholC. botulinum toxinD. isoflurophateE. phentolamine
Stem orderPatient detailsPresenting problemHistoryPhysical examLaboratory findingsInitial treatmentSubsequent findingsOption lead-in(No negative lead-in)
OptionsCover-up ruleHomogenous (tests, Rx)Balanced (↑ or ↓)PlausibleSimilar lengthAlphabetical
12
Typical / Ideal Exam Question Type F 1dA 52-old man undergoes a right total hip replacement. During the procedure, the patient experiences a flaccid muscle paralysis and a decrease in blood pressure following the administration of the neuromuscular blocking drug.Which of the following neuromuscular drugs was most likely administered in this patient?
A. atracuriumB. mivacuriumC. pancuroniumD. rocuroniumE. succinylcholineF. tubocurarine
Rules ?Two questionsSame stemNo return to 1st MCQNo extra informationAnswers not dependentDifferent lead in
OptionsCover-up ruleHomogenous (tests, Rx)Balanced (↑ or ↓)PlausibleSimilar lengthAlphabetical
Typical / Ideal Exam Question Type F 1e
A 52-old man undergoes a right total hip replacement. During the procedure, the patient experiences a flaccid muscle paralysis and a decrease in blood pressure following the administration of the neuromuscular blocking drug.At the end of the operation, a drug is administered to reverse the muscle paralysis. This drug was most likely which of the following?
A. atropine B. dantroleneC. neostigmineD. pancuroniumE. physostigmineF. succinylcholine
13
Drug Extensions I
nicardipinenifedipine-dipineCa Channel blockers
valsartanlosartan-sartanA-II blockers (ARBs)
rocuroniumatracurium-curiumNMJ blockers
simvastatinatorvastatin-vastatinHMG CoA reductaseinhibitors (statins)
lisinoprilcaptopril-prilACE inhibitors
terazosinprazosin-azosinAlpha1-blockers
atenololpropranolol-ololBeta-blockers
Drug Extensions II
ranitidinecimetidine-tidineH2-blockers
lansoprazoleomeprazole-prazoleProtein pump inhibitors
lorazepamalprazolam
diazepamloprazolam
-zepam-zolam
Benzodiazephines
dexamethasoneprednisone-soneCorticosteroids
reteplasestreptokinase-ase-plase
Thrombolytics
14
Drug Extensions III –Antibiotics/Antifungal Agents
cefdinir (3)cefaclor (2)cef-, ceph-Cephalosporins
levofloxacin (3)ciprofloxacin (2)-floxacinFluroquinolones
oxytetracyclinedoxycycline-cyclineTetracyclines
penicillin Vpenicillin G-cillinPenicillins
azithromycinerythromycin-thromycinMacrolides
streptomycingentamicin-micin,-mycin
Aminoglycosides
itraconazolemiconazole-azoleAntifungals
AcetaminophenAlcohol, isoniazidDisulfirum2E1
3A4
2D6
2C19
2C9
1A2
CCBs, statins,zolpidem, r-warfarin, prednisone, saquinavir, estrodiol-contraceptives
Carbamazepine, phenytoin, phenobarbital, rifampin, St. John’s wort
Diltiazem, grapefruit, verapamil, erythromycin, clarithromycin, ritonavir, ketoconazole
Carvedilol, amitriptyline, codeine, metoprolol
No significant inducersAmiodarone, cimetidine, diphenhydramine, ritonavir, fluoxetine
Omeprazole, phenytoin, phenobarbital
Carbamazepine, phenytoin, rifampin
Isoniazid, ritonavir,fluvoxamine
Carvedilol, ARB,s-warfarin, fluvastatin
Carbamazepine, phenytoin,phenobarbital, rifampin
Amiodarone, fluoxetine, metronidazole, trimethoprim/sulfamethoxazole
Caffeine, tizanidine, theophylline, r-warfarin
Carbamazepine, smoking, rifampin,phenobarbital
Amiodarone, cimetidine,ciprofloxacin, fluvoxamine
SubstratesInducersInhibitors
Main Cytochrome P450 Enzymes
15
Toxicity I
Na nitrite/Amyl nitrite, Hydroxycobalamin, Na Thiosulfate
Muscle weakness, hypotension, high anion gap metabolic acidosis, dysrhythmias, dyspnea, seizures, bitter almond odor, ↑plasma lactate
Cyanide
D-Penicillamine, (Dimercaprol)
Headache, tremor, rigidity, difficulty swallowing, irritable, confused, ↑AST/ALT, ↑ceruloplasmin(ferroxidase), renal toxicity, hemolysis, ab. pain
Copper
Hyperbaric oxygen, Oxygen
Headache, blurred vision, nausea, fatigue, red lips/fingers, ↑carboxyhemoglobin, tachycardia
Carbon monoxide
DimercaprolVomiting, abdominal pain, hyperhydrosis, ataxia, ↑HR, muscle weakness, ↑NE/EPI (↓metab.), red cheeks/fingers/toes, lethargy, renal toxicity
Mercury
DeferoxamineVomiting with blood, lethargic, ab. pain, ↑ferritin, high anion gap metabolic a. (prenatal supp.)
Iron
Fluid replacement and Dimercaprol
Vomiting, neuropathy, microcytic hypochromicanemia, diarrhea, alopecia, hyperpigmentation
Arsenic
Succimer(Ca-EDTA, Dimercaprol)
Vomiting, nausea, diarrhea, gingival bluish line (Burton line), weakness extensor muscles (wrist drop), microcytic hypochromic anemia, ab. pain
LeadTreatmentSymptomsAgent
Toxicity II
Stop drugDiffuse crackles, wheezing, pulmonary fibrosis, ↓HR, prolonged QT, wide QRS, hypothyroidism, cardiac depression, photosensitivity, bluish skin
Amiodarone
Stop drugEcchymoses, easy bruising, hematuria, anemia, dark stools, bleeding gums, ↑PT/INR
Warfarin
FomepizoleSlurred speech, nausea, vomiting, confusion, uncoordinated, lethargic, resting tremor, anion gap m. acidosis, ↑osmolar gap, intoxication
Ethylene glycol
FomepizoleNausea, vomiting, intoxication, blurred vision, ataxia, ↑plasma formic acid, high anion gap metabolic a., ↑osmolality gap
Methanol
Methylene blueHeadache, dizziness, chest pain, tachycardia, hypotension, methemoglobin, hemolysis
Nitrates
Cholinesterase inhibitor ie. Physostigmine
Dry mouth, blurred vision, mydriasis, tachycardia, flushing, delirium, convulsions, urinary retention, constipation, confusion
Belladonna alkaloids
Atropine and Pralidoxime (2-PAM)
sludgebam, muscle weakness, salivation sweating, miosis, lacrimation, urination, diarrhea, bronchospasm, bradyacardia, cramps
Organo-phosphate
TreatmentSymptomsAgent